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HIV/AIDS research in Brazil: the missing piece?

2006; Future Medicine; Volume: 1; Issue: 4 Linguagem: Inglês

10.2217/17460794.1.4.409

1746-0808

Mauro Schechter, Esper G. Kallás,

Syphilis Diagnosis and Treatment

Future VirologyVol. 1, No. 4 EditorialFree AccessHIV/AIDS research in Brazil: the missing piece?Mauro Schechter & Esper Georges KallasMauro Schechter† Author for correspondenceHospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, AIDS Research Laboratory, Av Brigadeiro Trompowski s/n lha do Fundão, Rio de Janeiro, RJ, 21941–590 Brazil. & Esper Georges KallasUniversidade Federal de São Paulo, Department of Medicine, Rua Mirassol 207, São Paulo, SP, 04044–010, Brazil. Published Online:25 Jul 2006https://doi.org/10.2217/17460794.1.4.409AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Figure 1. Number of reports issued by the Brazilian National Health Vigilance Agency (ANVISA) on clinical studies involving novel human products.Data obtained from [103].Brazil has been widely praised for being the first developing country to provide free and universal access to antiretroviral therapy, as well as for its direct and frank approach to the prevention of HIV/AIDS transmission. Unfortunately, Brazilian scientific output is not commensurate with its successes on treatment and prevention. In this editorial we argue that traditional explanations, such as cultural norms, the language barrier and lack of academic incentives do not fully justify this performance [1].The first case of AIDS in Brazil was diagnosed in 1982. By 1990, the number of cases had risen to 10,000, leading the World Bank to predict that Brazil would face an estimated 1.2 million cases of HIV/AIDS within one decade. By 2000, the estimated number of HIV-infected individuals was half that which had been predicted, leading the Brazilian response to the HIV/AIDS epidemic to be seen as an example to other developing countries.Brazil is currently a federal republic with a population of approximately 186 million [101]. It is the fifth most populous country in the world, with an average life expectancy of 71.6 years [102]. However, Brazil is still ranked 63rd on the Human Development Index, reflecting the large income disparities between rich and poor in the country [2].In the early 1980s, most HIV-infected individuals in Brazil were well-educated men, aged 20–44. At that time, the leading modes of HIV transmission were male homosexual sex and needle sharing between intravenous drug users. Over time, however, the epidemic has shifted into the general population and the number of heterosexually acquired infections has risen sharply [3]. At present, new infections and AIDS cases are increasingly frequent in women and in individuals with fewer years of formal education, a marker for lower socioeconomic status [4,5].Faced with dire predictions and the beginning of a generalized epidemic, a strong response was set in motion through a multisector strategy, which involved national and provincial governments, civil society, comprehensive prevention measures and healthsystem enhancement [6]. Together, these measures had a substantial impact on the course of the HIV epidemic, saved numerous lives and had a largely undocumented positive effect on the social and economic fabric of the country.Brazil's efforts to fight the epidemic began in earnest in 1985 when guidelines for the National AIDS Program (NAP) were established. The plan involved a multisector strategy and its potential effectiveness was strengthened greatly by the simultaneous implementation of several activities, including active involvement of civil society, balanced prevention and treatment efforts, direct and consistent messages and a practical, locally developed public health approach.From the beginning, the NAP implemented a comprehensive prevention strategy that consisted of the simultaneous execution of several components, including the promotion of condom use and of behavioral changes, encouraging voluntary counseling and testing, providing harm reduction programs for intravenous drug users, preventing mother-to-child transmission and providing support and education programs for people living with HIV/AIDS.The Brazilian response to the epidemic relied on a balanced approach, which included AIDS care and HIV prevention. It was the first developing country to provide free and universal access to antiretroviral therapy to all who need it. In 1991, zidovudine was made available on a limited scale. In 1996, a bill was passed that guaranteed free and universal access to treatment through the public healthcare system, including antiretroviral drugs. It is worth mentioning that in the 1990s, many (including the World Bank) were against providing HIV treatment to developing countries. They believed that, with limited resources, funds should be directed preferentially to prevention [7]. Thus, Brazil was the first country to realize that prevention and treatment are inextricably intertwined, an approach presently endorsed by the World Bank [8].The 1996 bill ensured the provision of drugs to all HIV-infected individuals who qualified for treatment according to locally developed guidelines. In order to provide this unprecedented access to treatment, it was necessary to scale up the healthcare system at various levels [9]. Treatment guidelines needed to be developed and updated periodically. Thus, an external and independent advisory expert committee was created in late 1996 and was given the responsibility to establish HIV treatment criteria [9]. It was (and still is) composed of local experts who meet periodically to review the latest scientific developments, to develop and adjust treatment guidelines accordingly.The estimated national prevalence of HIV infection in the adult population declined from 1.2% in the mid-1990s to 0.6% in 2001. Between 1996 and 2006, the number of individuals receiving free antiretroviral drugs increased from less than 20,000 to more than 170,000. Given its track record on prevention and treatment, it would seem reasonable that Brazil would have a commensurate scientific output. Unfortunately, this is not true as far as publications in high impact, peer-reviewed journals are concerned. Moreover, although Brazil is one of the leading countries in the number of abstracts submitted and accepted for presentation at the World AIDS Conferences, those accepted for oral presentations are quite limited, a proxy for relevance and quality.Several explanations have been suggested for this poor performance, including an academic system based largely on lifelong job stability, which is not dependent on scientific output, thus leading to a lack of will to publish in the international peer-reviewed literature, in addition to the language barrier and limited funding [1]. One might also add that the presence of a regulatory environment that is not conducive to the timely approval of projects and the cumbersome and bureaucratic difficulties in importing research supplies also impedes research performance. These deterrents should apply to all areas of science. Nonetheless, in other areas of human knowledge, in particular the health sciences, the Brazilian share of the world's scientific output stands out among developing countries, both in absolute numbers and the rate of growth over the previous few years [10]. Thus, other factors are likely to contribute to a scientific output that is not proportional to the Brazilian achievements in treatment and prevention of HIV/AIDS.In the 1980s, Brazil took several steps to discipline research involving human subjects in order to meet international standards for medical research. Particularly important was the creation of the National Committee on Research Ethics, which, besides certifying local institutional review boards, is responsible for providing final approval to projects that involve certain areas deemed to be particularly sensitive, such as studies that use new investigational drugs, are coordinated or funded by foreign institutions, involve genetic profiling or involve vulnerable populations (i.e., children, native Brazilian Indians or prisoners). Additionally, studies involving new drugs or new clinical laboratory tests require approval by the Ministry of Health Surveillance Agency (ANVISA), whose institutional mission is similar to the US FDA. Studies that involve genetically modified organisms and/or genetically engineered products also require approval by the National Biosafety Committee.Over the previous few years, the number of proposed clinical trials submitted for regulatory approval in Brazil has increased dramatically in all areas of medicine, particularly in HIV/AIDS. While in 1995, only 30 studies involving new drugs were proposed, in 2000, over 900 studies were submitted for evaluation (Figure 1) [103]. Unfortunately, regulatory processes have not maintained pace, leading to approval times that exceed 10 months on average. This long approval process has led to a slow but steady decrease in the number of clinical studies proposed to Brazilian institutions, particularly in highly competitive and fast moving areas, such as HIV/AIDS.Brazilian scientists have also been struggling with the bureaucracy necessary to acquire laboratory research supplies, especially those that need to be imported from other countries. Although some progress has been made by local manufacturers and research institutions to locally develop reagents and laboratory supplies, dependency on imports is still enormous. Moreover, importation of research supplies is, by and large, under the same rules and taxes that apply to most commercial products.Various governmental organizations are responsible for funding research. The National Council for Scientific and Technological Development (CNPq) is a foundation linked to the Ministry of Science and Technology, whose purpose is to promote and stimulate the country's scientific and technological development, and contribute to the formulation of national science and technology policy. It is presently estimated that approximately 30,000 active professionals hold a doctorate nationwide, and at least 22,000 of them gained their PhD with the help of CNPq. The 'Financiadora de Estudos e Projetos' (FINEP) is a state-owned agency that is also linked to the Ministry of Science and Technology. FINEP's main purpose is to promote and fund innovation and scientific research in companies, universities and research institutes, public or privately owned. The Campanha Nacional de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), is linked to the Ministry of Education. Created in 1951, CAPES main purpose is to ensure the existence of specialized personnel in sufficient quantity and of adequate quality to fulfill the needs of public and private enterprises that aim to assist in Brazil's development. Additionally, almost all Brazilian states have their own foundation to support research programs conducted at the local level.Over the previous few years the NAP has increased its investment in HIV/AIDS research through requests for applications (RFAs), mostly funded by the United Nations Educational, Scientific and Cultural Organization. This initiative began in 2001, and several RFAs have focussed on prevention, treatment and vaccines, including specific calls for behavioral aspects, social sciences, human rights, neglected populations and fostering research in certain Brazilian regions [11]. Arguably, the RFAs should have instead addressed research questions that Brazil would be uniquely positioned to respond to, particularly those with an operational nature, as indicated by the examples given below.As mentioned previously, in 1996 Brazil became the first developing country to provide universal and free access to antiretroviral therapy. In the public health system, patients are seen in a variety of settings, ranging from complex tertiary hospitals staffed by highly specialized infectious disease physicians to primary care facilities staffed by recently graduated interns. Obviously, the costs associated with the provision of care in such diverse environments are markedly different. Nonetheless, there are no systematic comparisons of differences in outcome, if any, and/or of the cost–effectiveness of care provided in these various settings. This type of operational information would be invaluable for many countries where a massive scaling-up of antiretroviral treatment is occuring at an impressive pace [12].The effectiveness of any treatment depends on the net balance of its desired versus adverse effects. Antiretroviral drugs act mostly by interfering with viral replication, thus allowing the immune system to recover, leading to a decrease in susceptibility to opportunistic infections. Thus, on a population basis, the positive impact of antiretroviral treatment can be estimated based on increased survival, the proportion of patients on treatment with undetectable plasma viral loads and on changes in the incidence of opportunistic infections.Several antiretroviral drugs are associated with serious adverse effects that may depend on genetic and environmental factors. Therefore, the frequency and severity of these side effects probably vary from country to country. For example, stavudine can cause lactic acidosis, a serious and frequently fatal condition, which is relatively rare in Western countries but can occur in up to 1% of South African patients [13]. Abacavir can cause a genetically determined hypersensitivity reaction that can be fatal, which occurs in 2–5% of patients in Western Europe and the USA, but appears to be rare in Africa. Both abacavir and stavudine are manufactured in Brazil and are part of regimens recommended by the NAP. Despite more than 200,000 Brazilians having so far received drugs from the public health system, there are limited data on the survival impact of treatment [14], the proportion of patients with undetectable plasma viral load [15], the impact of antiretroviral therapy on the incidence of opportunistic infections [16] or on the frequency of severe, drug-related adverse effects.There are also fairly limited data on a number of epidemiological issues that are of importance for planning prevention activities. For example, there is a striking scarcity of prospectively obtained data on risk factors for HIV infection [17,18].ConclusionsIn summary, Brazilian scientific output in the area of HIV/AIDS research is not commensurate with its success in treatment and prevention. Given that in other areas of the health sciences the Brazilian share of the world's scientific output stands out among developing countries, traditional explanations, such as the language barrier and lack of academic incentives, do not fully justify the poor performance in the area of HIV/AIDS. Among the chief additional reasons is the disproportional impact that the slow regulatory approval process has on more competitive areas, such as HIV/AIDS. Additionally, despite its laudable efforts to support research through focused RFAs, the NAP has failed to understand that one of the primary roles of science is to provide data that health authorities can use in order to make informed decisions. This has led to the absence of targeted funding to research questions that Brazil is uniquely positioned to respond to. The investigation of these questions would result in invaluable information that most likely could compete successfully for space in high-impact, peer-reviewed journals.Future perspectiveAs described previously, the Brazilian scientific output is not commensurate with its successes on treatment and prevention of HIV infection and AIDS. We believe that it is incumbent on all key stakeholders to take the necessary steps to revert the present situation. These, in turn, should emerge from iterative processes involving regulatory authorities, funding agencies and the scientific community. Topics to be discussed should include a means to decrease the bureaucracy involved and speed up the approval process, without compromising the quality of the review process. Equally important will be the review of pertinent legislation to facilitate access to laboratory research supplies. On a more general note, we believe it is important to re-address the present academic system, which is based largely on lifelong job stability that is not dependent on scientific output.Executive summary• Brazil is ranked 63rd on the Human Development Index, reflecting the large income disparities between rich and poor in the country.• In the mid-1980s, faced with dire predictions and the beginning of a generalized epidemic, a strong response to HIV/AIDS was set in motion.• Brazil was the first country to realize that prevention and treatment are inextricably intertwined.• Brazil was the first developing country to provide free and universal access to antiretroviral therapy.• The Brazilian scientific output on HIV and AIDS is not commensurate with its success in treatment and prevention.• Suggested explanations for the poor scientific performance include an academic system that is not dependent on scientific output, the language barrier and limited funding.• Other factors include a long approval process that is more acutely present in highly competitive and fast-moving areas, such as HIV and AIDS, and lack of a program that addresses research questions to which Brazil would be uniquely positioned to respond, particularly operational research questions.• We believe that it is incumbent on all key stakeholders to take the necessary steps to revert the present situation. 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